crossing96/oncoscreening huggingface dataset:
Limited predictive impact of tumor size dynamics on further tumor shrinkage after 4 cycles of first-line chemotherapy in patients with advanced urothelial carcinoma.	"PURPOSE: To investigate the correlation between tumor size changes during the initial 4 cycles of first-line chemotherapy and tumor shrinkage following 2 additional cycles of chemotherapy in patients with advanced urothelial carcinoma (aUC) who experienced disease control after initial chemotherapy. METHODS: We retrospectively reviewed 128 patients with aUC who received first-line chemotherapy. We analyzed 51 patients with disease control (stable disease or better) at the end of the fourth cycle. Of these, 47 patients received 1 to 2 additional cycles of chemotherapy, whereas the remaining patients underwent observation. For patients who received additional chemotherapy, the change in tumor size after additional chemotherapy (cycles 5-6) was defined as ""no shrinkage"" (tumor growth), ""minor shrinkage"" (no tumor growth or ≤10% reduction in tumor size), or ""shrinkage"" (>10% reduction in tumor size). Then, we investigated the relationship between the rate of tumor size change during the initial 4 cycles and that after additional chemotherapy. RESULTS: Of the patients who received additional chemotherapy, the change in tumor size was categorized as no shrinkage in 21 patients (44.7%), minor shrinkage in 18 patients (38.3%), and shrinkage in 8 patients (17%). Regarding predictors of tumor shrinkage after additional chemotherapy, the rate of tumor size change between the cycles 3 and 4 (area under the receiver operating characteristics curve = 0.642) was correlated with the trend of the tumor shrinkage (P = 0.009) and the likelihood of beneficial tumor shrinkage after additional chemotherapy (minor shrinkage + shrinkage; P = 0.02). However, the change in tumor size between cycles 1 and 2, cycles 1 and 4, or cycles 3 and 4 was not satisfactorily predictive of further tumor shrinkage because of substantial overlaps of the tumor size changes. CONCLUSIONS: Only a small subset of patients would have substantial tumor shrinkage by additional cycles after successful induction of 4 cycle chemotherapy. Tumor size dynamics during the initial 4 cycles of chemotherapy displayed limited ability to predict the subset of patients with further tumor shrinkage after additional chemotherapy. Therefore, it might be better to consider switch maintenance immunotherapy for patients who experience disease control after the fourth cycle of first-line chemotherapy."	bladder
Enfortumab vedotin in the treatment of urothelial cancers and beyond.	Enfortumab vedotin (EV) is the first antibody-drug conjugate approved for locally advanced or metastatic urothelial cancers (la/mUCs), a disease group historically associated with limited prognosis and therapeutic options. EV consists of monomethyl auristatin E, a microtubule-disrupting agent linked to an antibody targeting Nectin-4. In clinical trials, EV demonstrated high response rates and superior survival in the third-line setting for la/mUC compared with chemotherapy. Peripheral neuropathy and rash were among the most common serious adverse events. EV is currently approved in multiple countries for the treatment of la/mUC in the later-line setting. Ongoing trials seek to expand the indication for EV and to study therapeutic combinations with other agents.	bladder
"ThinPrep® imaging system-assisted vs manual screening of urinary cytology slides in the detection of the ""suspicious for high-grade urothelial carcinoma"" category."	BACKGROUND: The ThinPrep® Imaging System (TIS) is a Food and Drug Administration-approved review system for cervical cytopathology, where it has been shown to increase performance over manually reviewed slides. Application of the TIS to urinary cytology has only been reported in a single study, in 2013. METHODS: We aimed to compare the agreement of two cytotechnologists' and a pathologist's manual screening (dots) with the fields of view (FOVs) selected by the TIS. We also aimed to track cases in which the TIS could identify missed abnormals and reduce the false-negative fraction. Electronically marked TIS fields (EMTFs) suspicious for high-grade urothelial carcinoma (SHGUC) were controlled by follow-up cystoscopy and histology, where available. RESULTS: A total of 826 consecutive specimens were studied. Of those, 94 (11.4%) were unreadable by the TIS. There were 710 possible comparisons, of which 380 (53.5%) received no dot after manual screening. Of the 330 remaining slides, 149 (45.1%) had at least one dot matching with the TIS FOVs. After TIS reading, EMTFs were noted in 13 of 636 (2.0%) negative cytology cases. Surveillance showed that 3/13 (23.1%, 0.4% of the 710 possible comparisons) of those cases matched with high grade urothelial carcinoma (HGUC), whereas 6/13 (46.1%, 0.8% of the 710 possible comparisons) had negative follow-up at 24 months, and 4/13 (30.8%) were lost for follow-up. CONCLUSION: The TIS increases the detection rate of SHGUC cells, potentially leading to a slight decrease in the false-negative fraction, but at the expense of a slight but larger increase in the number of false-positive cases. These findings stress the importance of a careful approach to the evaluation of the FOVs.	bladder
Phase II trial of CV301 vaccine combined with atezolizumab in advanced urothelial carcinoma.	CV301 comprises recombinant poxviruses, Modified Vaccinia Ankara (MVA) and Fowlpox (FPV), encoding CEA, MUC-1, and co-stimulatory Molecules (TRICOM) ICAM-1, LFA-3, and B7-1. MVA-BN-CV301 is used for priming and FPV-CV301 is used for boosting. A Phase 2, single-arm trial was designed to evaluate CV301 plus atezolizumab as first-line treatment for cisplatin-ineligible advanced urothelial carcinoma (aUC) (Cohort 1) or progressing after platinum chemotherapy (Cohort 2). MVA-CV301 was given subcutaneously (SC) on Days 1 and 22 and FPV-CV301 SC from day 43 every 21 days for 4 doses, then tapered gradually over up to 2 years. Atezolizumab 1200 mg IV was given every 21 days. The primary endpoint was objective response rate (ORR). Overall, 43 evaluable patients received therapy: 19 in Cohort 1; 24 in Cohort 2; nine experienced ≥ Grade 3 therapy-related adverse events. In Cohort 1, one had partial response (PR) (ORR 5.3%, 90% CI 0.3, 22.6). In Cohort 2, 1 complete response and 1 PR were noted (ORR 8.3%, 90% CI 1.5, 24.0). The trial was halted for futility. Patients exhibiting benefit demonstrated T-cell response to CEA and MUC-1. The trial illustrates the challenges in the development of vaccines, which should be guided by robust preclinical data.	bladder
Survival outcomes of patients with muscle-invasive bladder cancer according to pathological response at radical cystectomy with or without neo-adjuvant chemotherapy: a case-control matching study.	OBJECTIVES: To assess survival of patients with muscle-invasive bladder cancer (MIBC) who underwent radical cystectomy (RC) with or without neo-adjuvant chemotherapy (NAC) according to the pathological response at RC. METHODS: 965 patients with MIBC (cT2-4aN0M0) who underwent RC with or without NAC were analyzed. Among the collected data were comorbidity, clinical and pathological tumor stage, tumor grade, nodal status (y)pN, and OS. Case-control matching of 412 patients was performed to compare oncological outcomes. Kaplan-Meier curves were created to estimate OS for patients who underwent RC with or without NAC, and for those with complete response (pCR), partial response (pPR), or residual or progressive disease (PD). RESULTS: Patients with a pCR or pPR at RC, with or without NAC, had better OS than patients who had PD (both p values < 0.001). Moreover, the incidence of pCR was significantly higher in patients receiving NAC prior to RC than in patients undergoing RC only (31% versus 15%, respectively; p < 0.001). Case-control matching displayed better OS of patients who underwent RC with NAC, median survival not reached, than of those who underwent RC only, median 4.5 years (p = 0.023). CONCLUSIONS: This study showed that patients with MIBC who underwent NAC with RC had a significant better OS than those who underwent RC only. The proportion of patients with a pCR was higher in those who received NAC and RC than in those who were treated by RC only. The favorable OS rate in the NAC and RC cohort was probably attributed to the higher observed pCR rate.	bladder
Uncovering additional predictors of urothelial carcinoma from voided urothelial cell clusters through a deep learning-based image preprocessing technique.	BACKGROUND: Urine cytology is commonly used as a screening test for high-grade urothelial carcinoma for patients with risk factors or hematuria and is an essential step in longitudinal monitoring of patients with previous bladder cancer history. However, the semisubjective nature of current reporting systems for urine cytology (e.g., The Paris System) can hamper reproducibility. For instance, the incorporation of urothelial cell clusters into the classification schema is still an item of debate and perplexity among expert cytopathologists because several previous works have disputed their diagnostic relevance. METHODS: In this work, an automated preprocessing tool for urothelial cell cluster assessment was developed that divides urothelial cell clusters into meaningful components for downstream assessment (ie, population-based studies, workflow automation). RESULTS: In this work, an automated preprocessing tool for urothelial cell cluster assessment was developed that divides urothelial cell clusters into meaningful components for downstream assessment (ie, population-based studies, workflow automation). Results indicate that cell cluster atypia (i.e., defined by whether the cell cluster harbored multiple atypical cells, thresholded by a minimum number of cells), cell border overlap and smoothness, and total number of clusters are important markers of specimen atypia when considering assessment of urothelial cell clusters. CONCLUSIONS: Markers established through techniques to separate cell clusters may have wider applicability for the design and implementation of machine learning approaches for urine cytology assessment.	bladder
Urodynamic assessment and quality of life outcomes of robot-assisted totally intracorporeal radical cystectomy and orthotopic neobladder for bladder cancer: a preliminary study.	PURPOSE: Few data exist regarding the functional outcomes of robot-assisted radical cystectomy (RARC) with intracorporeal orthotopic neobladder. The aim of this study was to evaluate the urodynamic and functional outcomes in patients undergoing RARC and totally intracorporeal orthotopic neobladder for bladder cancer. METHODS: In this monocentric, observational study carried out between 2016 and 2020, consecutive patients undergoing RARC and intracorporeal orthotopic neobladder in the Department of Urology, Pitié-Salpêtrière Hospital, were included. Reconstruction was totally intracorporeal Y-shaped neobladder. Main outcomes were urodynamic findings 6 months post-surgery, continence and quality of life (QoL). Continence was defined by no pad or one safety pad. International Consultation on Incontinence Questionnaire (ICIQ), International Index of Erectile Function questionnaire (IIEF-5) and Bladder Cancer Index (BCI) scores were recorded. RESULTS: Fourteen male patients were included (median age: 64 years [IQR 54-67]. Median maximal neobladder cystometric capacity was 495 ml [IQR 410-606] and median compliance was 35.5 ml/cm H(2)O [IQR 28-62]. All patients had post-void residual volume < 30 ml, except for three (22%) who required clean intermittent-self catheterisation. Daytime continence was achieved in 10 patients (71%) and night-time continence in two (14.3%). Median ICIQ score was 7 [IQR 5-11]. Postoperative erectile function was present in 7% of patients (mean IIEF-5 = 5 [IQR 2-7]). Thirteen patients (93%) were satisfied with their choice of neobladder. CONCLUSION: RARC with totally intracorporeal orthotopic neobladder for bladder cancer provides satisfactory urodynamic results and good QoL. These findings should be confirmed long-term.	bladder
Estimation of the Number of Individuals Living With Metastatic Cancer in the United States.	BACKGROUND: The purpose of this study was to estimate the number of individuals living with metastatic breast, prostate, lung, colorectal, or bladder cancer or metastatic melanoma in the United States using population-based data. METHODS: A back-calculation method was used to estimate the number of individuals living with metastatic cancer for each cancer type from US cancer mortality and survival statistics from the Surveillance, Epidemiology, and End Results registries. The percentages of those living with metastatic cancer who advanced to metastatic disease from early stage cancer vs who were diagnosed with metastatic cancer de novo were calculated. One- and 5-year relative survival rates for de novo metastatic cancer were compared by year of diagnosis to assess time trends in survival. RESULTS: It is estimated that, in 2018, 623 405 individuals were living with metastatic breast, prostate, lung, colorectal, or bladder cancer, or metastatic melanoma in the United States. This number is expected to increase to 693 452 in 2025. In 2018, the percentage of metastatic cancer survivors who were initially diagnosed with early stage cancer and advanced to metastatic cancer ranged from 30% for lung cancer to 72% for bladder cancer. CONCLUSIONS: This study demonstrates increasing numbers of individuals living with metastatic cancer of the 6 most common cancer types in the United States. This information is critical for informing the allocation of research efforts and healthcare infrastructure needed to address the needs of these individuals.	bladder
Design, synthesis, and biological evaluation of novel dual inhibitors of heat shock protein 90/mammalian target of rapamycin (Hsp90/mTOR) against bladder cancer cells.	In this study, a novel class of thieno [2,3-d] pyrimidine derivatives containing resorcinol and morpholine fragments as Hsp90/mTOR dual inhibitors was designed, synthesized, and evaluated. In vitro anti-tumor assay results: the obtained compounds demonstrated effectiveness in suppressing the enzymatic activities of the Hsp90 and mTOR and inhibiting the proliferation of J82, T24, and SW780 cancer cell lines. Among these dual inhibitors, the most potent compound 17o, confirmed remarkable inhibitory activities on Hsp90, mTOR, and SW780 cell. Furthermore, the molecular dynamics simulation and a panel of mechanism studies revealed that inhibitor 17o suppressed the proliferation of SW780 cells through the over-activation of the PI3K/AKT/mTOR pathway regulated by mTOR inhibition and apoptosis regulated by the mitochondrial pathway. In subcutaneous J82 xenograft models, the compound 17o also presented considerable in vivo anti-tumor activity. Therefore, our investigations highlight that a new-found dual Hsp90/mTOR inhibitor by rational drug design strategies could be a promising lead compound for targeted bladder cancer therapy and deserves further studies.	bladder
Tumor expression of Nectin-1-4 and its clinical implication in muscle invasive bladder cancer: An intra-patient variability of Nectin-4 expression.	There is limited evidence regarding the tumor expression of nectins and their clinical implications in muscle invasive bladder cancer. Herein, we evaluated expression of Nectins 1-4 in 64 patients with muscle invasive bladder cancer who underwent radical cystectomy using a histochemical scoring method (H-score; immunohistochemical staining intensity multiplied by the percentage of positive-staining cells). The cutoff values were defined based on the median H-scores. Of the 64 patients, 45 (70%) had residual tumors in radical cystectomy specimens, while 13 (20%) had lymph node metastasis. The median (interquartile range) H-scores of Nectin-1, - 2, - 3, and - 4 expression were 0 (0-10), 80 (30-180), 5 (0-30), and 100 (33-160), respectively. The Nectin-4 H-score of the neuroendocrine variant was significantly lower than that of pure urothelial carcinoma (P = 0.015). Post-neoadjuvant chemotherapy pathological response (<ypT2N0 residual disease and pN-negative) was achieved in 18 (49%) of the 37 patients who received neoadjuvant chemotherapy. Clinical stage II, not Nectin expression, was an independent factor associated with pathological response (P = 0.019, adjusted odds ratio 6.9, vs stage III/IV). There was no correlation in Nectin-4 tumor expression between transurethral resection and matched radical cystectomy specimens and between radical cystectomy specimens and matched lymph node metastatic lesions. However, there was a significant decrease in Nectin-4 expression in post-neoadjuvant chemotherapy radical cystectomy specimens compared to pre-neoadjuvant chemotherapy transurethral resection specimens (P = 0.008). Given the downregulation of Nectin-4 by chemotherapy and the significant discrepancy between radical cystectomy and matched lymph node metastasis specimens, baseline primary tumors may not be a suitable material for evaluating Nectin-4 expression and its potential as a predictive biomarker for enfortumab vedotin treatment.	bladder
Preoperative monocyte-to-lymphocyte ratio as a potential predictor of bladder cancer.	OBJECTIVES: The aim of this study was to investigate the role of preoperative Monocyte-to-Lymphocyte ratio (MLR) as a potential predictor of bladder cancer (BC). METHODS: Clinical data of patients who underwent TURBT at our institution between 2017 and 2021 were collected and retrospectively analysed. MLR was obtained from preoperative blood analyses performed within 1 month from hospital admission. The association of MLR with different clinic-pathological features obtained from histological reports was further analysed. Statistical analysis was performed using the Kruskal Wallis test for non-parametric variables, assuming p<0.05 as statistically significant. RESULTS: 510 patients were included in the study (81% males, 19% females), with a mean age of 71.66 ± 11.64 years. Mean MLR was higher in patients with any-type bladder cancer, reporting an MLR of 0.41 ± 0.11 compared to 0.38 ± 0.43 in patients without bladder cancer (p=0.043). In the subsequent comparison among low-grade and high-grade bladder cancer, MLR did not report statistically significant differences, with 0.29 ± 0.12 for low-grade BC and 0.51 ± 0.81 for high-grade BC (p=0.085). CONCLUSIONS: Our findings reported elevated preoperative MLR should be considered a potential biomarker predicting malignancy for bladder tumours. Furthermore, research are necessary to assess its role in discerning low-grade from high-grade patients.	bladder
EphrinB2 Inhibition and Pembrolizumab in Metastatic Urothelial Carcinoma.	PURPOSE: Patients with metastatic urothelial carcinoma have poor prognosis after failure of standard first-line chemotherapy. Immune check point programmed death 1-programmed death ligand 1 antibodies have low response rates and thus there exists a major unmet need. MATERIALS AND METHODS: In this phase II trial, patients with metastatic urothelial carcinoma that recurred or progressed after platinum-based chemotherapy received soluble EphB4-human serum albumin (sEphB4-HSA) in combination with pembrolizumab. The primary end points were tolerability and overall survival (OS). The secondary end points were progression-free survival (PFS), objective response rate (ORR), duration of response, and toxicity. The expression of sEphB4-HSA target EphrinB2 was correlated with outcomes. RESULTS: Seventy patients were enrolled. The median follow up was 22.9 months (range, 1.3-54.7). The regimen had acceptable toxicity. In the intent-to-treat analysis (N = 70), the median OS was 14.6 months (95% CI, 9.2 to 21.5). Twenty-six (37%) patients had an objective response (95% CI, 26 to 48). The median PFS was 4.1 (95% CI, 1.5 to 5.7) months. Forty-six (66%) patients expressed EphrinB2, and among them, the median OS was 21.5 months (95% CI, 12.4 to not reached), the ORR was 52% (95% CI, 37 to 67), including a complete response rate of 24% (11 of 46; 95% CI, 12 to 36). The median PFS was 5.7 (95% CI, 2.7 to 27.9) months. Response was maintained at 6, 12, and 24 months in 88%, 74%, and 69% of the patients, respectively. CONCLUSION: The combination of sEphB4-HSA and pembrolizumab appears synergistic with improved OS and ORR compared with historical data for programmed death 1/programmed death ligand 1 monotherapy.	bladder
The Clinicopathological and Prognostic Value of NLR, PLR and MLR in Non-Muscular Invasive Bladder Cancer.	BACKGROUND: The clinicopathological and prognostic relevance of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and monocyte/lymphocyte ratio (MLR) in non-muscular invasive bladder cancer (NMIBC) was investigated. METHODS: All patients who underwent transurethral resection of bladder tumor (TURBT) and postoperative intravesical chemotherapy had their peripheral blood levels of NLR, PLR, and MLR quantified. The preoperative peripheral blood levels of NLR, PLR, and MLR were analyzed in patients with G1, G2, and G3 NMIBC. A total of 208 patients was divided into poor prognosis (PP, with recurrence, n=51) and good prognosis (GP, no recurrence, n=157) groups, according to whether the recurrence of NMIBC was observed at 1-year follow-up after treatment. Univariate and multivariate logistic regression analyses were performed to evaluate the prognostic factors in NMIBC. In addition, receiver operating characteristic (ROC) curves were used to analyze the prognostic performance of NLR, PLR, and MLR in NMIBC. RESULTS: The preoperative peripheral blood level of PLR was significantly increased in patients with G3 NMIBC compared with that in patients with G1 (p < 0.05) and G2 NMIBC (p < 0.05). The results of univariate and multivariate logistic regression analyses showed that the tumor diameter, differentiation grade, and preoperative peripheral blood levels of NLR, PLR, and MLR were independent prognostic factors for NMIBC recurrence (p < 0.05). Compared with the NMIBC patients without recurrence, 3.490%, 177.575% and 3.175% were determined as the optimum prognostic cutoffs for NLR, PLR, and MLR, respectively. ROC curve was used to evaluate the sensitivity, specificity, and area under the curve (AUC) of NLR, PLR, MLR, and combinations. In contrast to NLR, PLR, or MLR, the combination of NLR, PLR, and MLR (AUC 0.758, sensitivity 66.70%, specificity 89.80%,Youden index 0.565) improved the prognostic performance in the discrimination of NMIBC patients with recurrence from thosewithout recurrence. CONCLUSIONS: The preoperative peripheral blood levels of NLR, PLR, and MLR, which were closely related to the grade and recurrence of NMIBC, were easy to detect and inexpensive. Moreover, these three factors showed the potential for auxiliary prognostic evaluation of NMIBC, wherein the combination than individual values exhibited better prognostic performance.	bladder